Glomerular filtration and tubular reabsorption of albumin in preproteinuric and proteinuric diabetic rats.
Glomerular filtration and tubular reabsorption of albumin in preproteinuric and proteinuric diabetic rats.
复制标题
前蛋白尿和蛋白尿糖尿病大鼠的肾小球滤过和肾小管白蛋白重吸收。
DOI：
10.1172/jci116638
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Blantz,RC
中科院分区：
文献类型：
--
作者：
Tucker,BJ;Rasch,R;Blantz,RC
微量白蛋白尿（26-250 mg/d）被认为是人类胰岛素依赖型糖尿病（IDD）初期糖尿病肾病的指标。然而，在观察到微量白蛋白尿之前，IDD患者的肾小球改变，如肾小球基底膜糖基化和肾小球超滤，可能导致白蛋白排泄增加之前白蛋白滤过增加。在链脲佐菌素（65 mg/kg体重，i. v.）在糖尿病发作后7-10天（未治疗）和50-70天（小剂量胰岛素控制不良），与非糖尿病对照组相比，每种情况下的其他大鼠接受急性赖氨酸治疗，以防止肾小管蛋白重吸收。测量肾皮质中的尿白蛋白排泄量和非血管白蛋白分布体积，并与间质间隙和近端小管的形态测量进行比较，以评估近端小管中白蛋白的细胞内摄取。麻醉下的尿白蛋白排泄量在7-10-d IDD组与对照组无差异（19 +/- 3 vs. 20 +/- 3 μ g/min），但在50-70-d IDD组增加（118 +/- 13 μ g/min，P < 0.05）。赖氨酸治疗导致7-10天IDD患者的白蛋白排泄量增加（67 ± 10微克/分钟，P < 0.05），但对照组（30 ± 6微克/分钟）或50-70天IDD患者（126 ± 11微克/分钟）的白蛋白排泄量没有增加。与对照组（2.2 ± 0.1ml/min）相比，IDD 7-10 d组（2.7 ± 0.1ml/min）和IDD 50-70 d组（2.6 ± 0.1ml/min）的肾小球滤过率均显著增加（P <0.05）。与对照组（1.4 +/- 0.3 mg%）相比，IDD患者早期计算的尿间隙白蛋白浓度增加，7-10-d IDD患者为2.5 +/- 0.4 mg%，50-70-d IDD患者为4.9 +/- 0.6 mg%。在糖尿病早期白蛋白排泄增加之前，白蛋白滤过的增加超过了超滤。在50-70天的IDD中，肾小管对白蛋白的绝对重吸收减少，与近端小管刷状缘高度的降低相关。图片
Microalbuminuria (26-250 mg/d) is considered to be an indicator of incipient diabetic nephropathy in humans in insulin-dependent diabetes (IDD). However, before microalbuminuria is observed, glomerular alterations, such as glycosylation of the glomerular basement membrane and glomerular hyperfiltration, in IDD may result in increased filtration of albumin before any observed increase in albumin excretion. Glomerular and tubular albumin kinetics were examined in streptozotocin (65 mg/kg body wt, i.v.) diabetic, Munich-Wistar rats at 7-10 (untreated) and 50-70 d (poorly controlled with small doses of insulin) after the onset of diabetes and compared with nondiabetic controls. Additional rats in each condition received acute lysine treatment to prevent tubular protein reabsorption. Urinary albumin excretion and nonvascular albumin distribution volumes were measured in the renal cortex and compared with morphometric measurements of interstitial space and the proximal tubule to assess intracellular uptake of albumin in the proximal tubule. Urinary albumin excretion under anesthesia was not different in 7-10-d IDD versus controls (19 +/- 3 vs. 20 +/- 3 micrograms/min) but increased in the 50-70-d IDD (118 +/- 13 micrograms/min, P < 0.05). Lysine treatment resulted in increased albumin excretion compared with respective nontreatment in 7-10-d IDD (67 +/- 10 micrograms/min, P < 0.05) but not in controls (30 +/- 6 micrograms/min) or in 50-70-d IDD (126 +/- 11 micrograms/min). Glomerular filtration rate was increased both in 7-10-d IDD (2.7 +/- 0.1 ml/min, P < 0.05) and in 50-70-d IDD (2.6 +/- 0.1 ml/min, P < 0.05) compared with control (2.2 +/- 0.1 ml/min). Calculated urinary space albumin concentrations increased early in IDD with 2.5 +/- 0.4 mg% in 7-10-d IDD and 4.9 +/- 0.6 mg% in 50-70-d IDD compared with control (1.4 +/- 0.3 mg%). The increase in filtration of albumin is in excess of that attributable to hyperfiltration before increased albumin excretion early in diabetes. In 50-70-d IDD, absolute tubular reabsorption of albumin is decreased, correlating to the decrease in brush border height of the proximal tubule.Images